Howard Crawford Laboratories at University of Michigan

Immunotherapy

The Pasca di Magliano, Lyssiotis, Frankel and Crawford laboratories at the University of Michigan have teamed up to devise ways to make immunotherapy effective in fighting pancreatic cancer. Dr. Pasca di Magliano has discovered that macrophages, a specialized inflammatory cell, are the cells primarily responsible for establishing the immune suppressed environment by both sending signals to immune cells to ignore the tumor and then signaling to the tumor cells to have them express high levels of PD-L1.

 

In turn, the tumor cells instruct the macrophages to also make PD-L1. In an attempt to disrupt this cycle, Dr. Crawford has identified one of the primary molecules the macrophages use to turn on tumor cell PD-L1, known as HBEGF. Meanwhile, Dr. Lyssiotis has found that tumor cell metabolites are responsible for telling the macrophages to make PD-L1. With this knowledge in hand, Dr. Frankel, a surgeon who specializes in immunotherapy research, is involved in translating these observations to the clinic, combining immune checkpoint inhibitors with therapies to disrupt the cellular crosstalk responsible for establishing the immunosuppressive environment in preclinical models of human pancreatic cancer.

Immunotherapy Team Members

Marina Pasca di Magliano, PhD

Costas Lyssiotis, Phs

Timothy Frankel, MD

 

  • Early Detection Screening
    In pursuit of the goal of developing a practical, minimally invasive, method of detecting pancreatic cancer at its earliest stages, the Crawford laboratory has teamed up with the laboratory of Dr. Lonnie Shea, Chair of the Department of Biomedical Engineering at the University of Michigan.

    Dr. Shea has invented a microporous scaffold that, when implanted beneath the skin, attracts tumor cells that have separated from the primary tumor and entered the blood stream, presumably in an attempt to metastasize to distant organs.

    However, work by laboratories at the University of Michigan and others have found that simply finding potentially neoplastic cells in the bloodstream does not by itself indicate the presence of cancer, as they can also be associated with benign, non-life threatening conditions.

    The Crawford laboratory has identified a rare cellular subtype derived from pancreatic tumors whose presence in the bloodstream is highly associated with cancer development and early metastasis.

    Combined with the use of the Shea laboratory’s implants to attract them, the Crawford laboratory is monitoring occupation of the implant by this aggressive cell type in preclinical models to predict the presence of early cancer at the primary site.

    Team Member of Early Detection Project: Lonnie Shea, PhD
News